title: Plasma homocysteine, methionine and S-adenosylhomocysteine levels following high-dose methotrexate treatment in pediatric patients with acute lymphoblastic leukemia or Burkitt lymphoma: association with hepatotoxicity.
abstract: This study aimed to investigate: (i) changes of plasma homocysteine, methionine and S-adenosylhomocysteine levels following high-dose methotrexate (HD-MTX) treatment and (ii) the correlation of these sulfur-containing amino acids with MTX-induced hepatotoxicity. Fifteen pediatric patients with acute lymphoblastic leukemia and one patient with Burkitt lymphoma, with a total of 26 treatment courses of HD-MTX, were enrolled. Homocysteine levels increased at 24 h after HD-MTX treatment, and showed marginal decreases at 48 and 72 h. Methionine levels showed a biphasic pattern, i.e. an initial decrease at 24 h followed by increases at 48 and 72 h. S-adenosylhomocysteine exhibited a marginal decrease at 24 h. Changes of homocysteine exhibited significant correlation only with a maximum increase of alanine aminotransferase or total bilirubin from baseline. This study has demonstrated, for the first time, simultaneous changes of plasma homocysteine, methionine and S-adenosylhomocysteine following HD-MTX. The potential of homocysteine as a marker of hepatotoxicity is also presented.
authors.affiliation: Department of Human Life and Environment, Nara Women's University , Nara , Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Kubota
authors.forename: Rieko
authors.initials: R
authors.lastname: Nakata
authors.forename: Souichi
authors.initials: S
authors.lastname: Adachi
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Watanabe
authors.forename: Toshio
authors.initials: T
authors.lastname: Heike
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Takeshita
authors.forename: Midori
authors.initials: M
authors.lastname: Shima
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D002051:Burkitt Lymphoma / Q000097:blood* / Q000188:drug therapy*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D008715:Methionine / Q000097:blood*; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood* / Q000188:drug therapy*; D012435:S-Adenosylhomocysteine / Q000097:blood*
chemical_list: D000964:Antimetabolites, Antineoplastic; D006710:Homocysteine; D012435:S-Adenosylhomocysteine; D008715:Methionine; D008727:Methotrexate
keywords: Children; S-adenosylhomocysteine; hepatotoxicity; high-dose methotrexate; homocysteine; methionine